How organisms respond to light and how photosensory receptors mediate light responses are basic questions in biology. Our long-term goal is to find the molecular explanation of these questions, using the cryptochrome photoreceptor as a model system. Cryptochromes (CRY) are the blue/UV-A light receptors and/or core components of the circadian oscillator found in all evolutionary lineages including human. My laboratory focuses on the study of plant cryptochromes. In the previous funding periods, we discovered two major CRY2 signal transduction mechanisms: the CIB1 (Cryptochrome-Interacting bHLH 1)-based transcription- regulatory mechanism and SPA1/COP1 (Suppressor of Phytochrome A 1/Constitutive Photomorphogenesis 1)-based proteolysis-regulatory mechanism. More recently, we identified a CIB-interacting protein FOF1 (F-box of Flowering 1) responsible for the blue light-regulated degradation of CIB1; two new blue light-specific CRY2-interacting proteins: PRR5 (Pseudo Response Regulator 5) that is a core protein of the circadian clock, and a novel protein BIC1 (Blue- light Inhibitor of CRYs 1) tha suppresses blue light-dependent phosphorylation, degradation, and activities of CRY1 and CRY2. Based on these discoveries and newly developed tools, we propose to study three key issues of light signal transduction: the photochemical mechanism underlying photoexcitation of the CRY photoreceptor, mechanisms governing the function and regulation of the CRY complexome, and the mechanism underlying a novel coding sequence (CDS)-dependent blue light regulation of CRY2 expression.